Assessment of Leishmanicidal and Trypanocidal Activities of Aliphatic Diamine Derivatives
Autor: | Rafael Luis Kessler, Iriane Eger, Maiko L. Tonini, Mauro V. de Almeida, Raquel Brandt Giordani, José Angelo S. Zuanazzi, Celina Noriko Yamanaka, Celso O. Rezende, Mário Steindel, Milene Höehr de Moraes, Débora R. R. P. Araujo |
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Rok vydání: | 2013 |
Předmět: |
Cell Survival
Trypanosoma cruzi Bone Marrow Cells Diamines Biology Nitric Oxide Biochemistry Mice parasitic diseases Drug Discovery medicine Animals Amastigote Leishmania Membrane Potential Mitochondrial Pharmacology Mice Inbred BALB C Tumor Necrosis Factor-alpha Macrophages Organic Chemistry Depolarization biology.organism_classification Trypanocidal Agents Leishmania braziliensis In vitro Mechanism of action Benznidazole Molecular Medicine medicine.symptom medicine.drug |
Zdroj: | Chemical Biology & Drug Design. 82:697-704 |
ISSN: | 1747-0277 |
Popis: | Leishmanicidal and trypanocidal activity of seventeen lipophilic diamines was evaluated in vitro against Leishmania braziliensis, L. chagasi, and Trypanosoma cruzi. Twelve compounds presented anti-Leishmania and six showed anti-T. cruzi amastigote activity. Compound 14 (N-tetradecyl-1,4-butanediamine) was the most active against both L. braziliensis (IC50 = 2.6 μm) and L. chagasi (IC50 = 3.0 μm) which showed a selectivity index (SI) >100. N-decyl-1,6-hexanediamine (compound 9) presented an IC50 = 1.6 μm and SI >187 and was over six times more potent than the reference drug benznidazole against T. cruzi. Treatment of infected or uninfected macrophages with compounds 9 and 14 did not induce significant TNFα and NO production. Four compounds (15, 16, 22, and 23) inhibited 78.9%, 77.7%, 83.7%, and 70.1% of rTRLb activity, respectively, and compound 23 inhibited 73.3% of rTRTc activity at 100 μm. A concentration-dependent effect on mitochondrial membrane depolarization was observed in T. cruzi epimastigotes treated with compound 9, suggesting this mechanism may be involved in the trypanocidal effect. On the contrary, in L. braziliensis promastigotes treated with compound 14, no mitochondrial depolarization was observed. Our results demonstrate that N-decyl-1,6-hexanediamine and N-tetradecyl-1,4-butanediamine are promising molecules for the development of novel leading compounds against T. cruzi and Leishmania spp., particularly given a possible alternative mechanism of action. |
Databáze: | OpenAIRE |
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